1.Effect of wogonin on nerve injury in rats with diabetic cerebral infarction
Huanhuan WANG ; Panpan LIANG ; Jinshui YANG ; Shuxian JIA ; Jiajia ZHAO ; Yuanyuan CHEN ; Qian XUE ; Aixia SONG
Chinese Journal of Tissue Engineering Research 2025;29(11):2327-2333
BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.
2.Modified Palmer classification of traumatic triangular fibrocartilage complex injury based on MRI
Canhua GAO ; Guoshi LÜ ; Zhijun HAO ; Yadong KANG ; Yanxia HAO ; Lei ZHENG
Journal of Practical Radiology 2024;40(1):88-91
Objective To classify traumatic triangular fibrocartilage complex(TFCC)injury based on 3.0T MR.Methods A total of 46 patients with definite history of wrist trauma admitted were collected.All patients underwent MRI scanning within 3 days after trauma,and the MRI findings were classified as follows according to the Palmer classification criteria:the focal structures of triangular fibro-cartilage(articular disc)(TFC)injury,the horizontal of the articular disc tear,injuries of ulnar styloid attachment and ulnar fovea attach-ment in TFC,ulnolunate and ulnotriquetral ligaments injuries,injury of the radial sigmoid notch junction,meniscal homologous inju-ry.The presence of TFCC injury was eventually confirmed by surgery in all patients.Results Of 46 patients,38 patients could be classified by Palmer,and there were 10 cases with type ⅠA,23 cases with type ⅠB,3 cases with type ⅠC and 2 cases with type ⅠD.A total of 8 patients were not suitable for Palmer type,and there were 3 patients with horizontal tears in the articular disc and 5 patients with meniscus homologous injuries.Conclusion The 3.0T MR can not only show various subtypes of Palmer classification,but also refine and supplement the classification based on the original classification,such as the injuries of ulnar styloid attachment and ulnar fovea attachment at the ulnar end of the articular disc,horizontal tear of the articular disc,meniscus homologous injury,etc.
3.Intra-and peri-tumoral radiomics model for predicting the response to concurrent chemoradiotherapy in cervical squamous cell carcinoma based on dynamic contrast-enhanced MRI
Yaying SU ; Dan ZHAO ; Zhiying PANG ; Fei YANG ; Shujun CUI
Journal of Practical Radiology 2024;40(3):411-416
Objective To investigate the correlation between intra-and peri-tumoral radiomics features and the response to con-current chemoradiotherapy(CCRT)in cervical squamous cell carcinoma,and to explore the difference of predictive performance between 2D and 3D radiomics models.Methods The imaging data of 132 patients were analyzed retrospectively and randomly divided into training set(n=92)and validation set(n=40).Radiomics features were extracted based on the dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI),the correlation analysis and least absolute shrinkage and selection operator(LASSO)algorithm were used for dimensionality reduction and screening,then the radiomics score was calculated and the logistic model was constructed.The receiver operating characteristic(ROC)curve,internal validation of Bootstrap and Brier score were used to evaluate the discrimina-tion and calibration of the model,and the improvement in predictive performance of 3D model compared with 2D model was evaluated by the integrated discrimination improvement(IDI).Results In the training set,the ROC curve showed that the area under the curve(AUC)of the models(2D-intratumoral,3D-intratumoral,3D-peritumoral,3D-combined)ranged from 0.774 to 0.893.The internal validation of Bootstrap showed the AUC were 0.772,0.860,0.847 and 0.888,respectively,while in the validation set,the AUC were 0.757,0.849,0.824 and 0.887,respectively.The Brier scores indicated that the models were well calibrated.In the training set and the validation set,the IDI values were 0.155 and 0.179,respectively,and the differences were statistically significant(P<0.05).Conclusion The radiomics analysis based on the tumor volume can fully explore the tumor heterogeneity.The intra-and peri-tumoral radiomics combined model shows the best predictive performance,which is important to assist clinicians in developing individualized therapies.
4.Huangqi Yanghe Decoction regulates PI3K/AKT/NF-κB signaling pathway to promote wound healing in diabetes foot ulcer rats
Yaling BAO ; Hui LEI ; Jun MA ; Xinmei ZHAO
Tianjin Medical Journal 2024;52(3):266-272
Objective To explore the effect of Huangqi Yanghe Decoction on wound healing of diabetic foot ulcer(DFU)rats based on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/nuclear factor-κB(NF-κB)signal pathway.Methods DFU rat model was constructed,and 48 rats successfully modeled were randomly divided into the model group,the Huangqi Yanghe Decoction low(8.5 g/kg)group,the Huangqi Yanghe Decoction high(17 g/kg)dose group and the Huangqi Yanghe Decoction high dose(17 g/kg)+LY294002(PI3K/AKT pathway inhibitor,0.3 mg/kg)group.There were 12 rats in each group.Another 12 rats were selected as the control group.Rats in each group were given corresponding drug intervention for 4 weeks.After the 14th and 28th day-administration,the general state and wound changes of rats were observed,and the wound healing rate was calculated.The fasting blood glucose(FBG)level of rats was measured,and the percutaneous partial pressure of oxygen(TcpO2)of tissue around the wound was detected.Serum levels of vascular endothelial growth factor(VEGF),hypoxia inducible factor-1α(HIF-1α),C-reactive protein(CRP)and interleukin(IL)-6 were determined by enzyme linked immunosorbent assay.Histopathological changes of the wound were observed by hematoxylin-eosin staining.Immunohistochemical staining was used to measure the microvascular density of rat wound tissue.The protein expression levels of PI3K,phosphorylated PI3K(p-PI3K),AKT,phosphorylated AKT(p-AKT),NF-κB p65,phosphorylated NF-κB p65(p-NF-κB p65)and NF-κB inhibitory protein α(IκB-α)in rat wound tissue were determined by Western blot assay.Results Rats in the control group had smooth hair color,normal diet,drinking water and excretion,more active,wound healing fast,less inflammatory reaction in wound tissue,and there were more new blood vessels.Fibroblasts and collagen matrix were abundant in granulation tissue.In the model group,the fur color of rats was dull and matte,and the activity was reduced.The symptoms of polydipsia,polyphagia and polyuria were appeared in the model group,the wound color was dark,and edema and ulcer appeared in the surrounding tissue,a large number of inflammatory cells infiltrated in the wound tissue,accompanied by tissue necrosis and exudation,fewer neovascularization and fibroblasts were observed.Wound healing rate,TcpO2 in wound surrounding tissue,serum VEGF,HIF-1α,microvascular density,p-PI3K,p-AKT and IκB-α protein expression levels in wound tissue were decreased,and FBG,serum CRP,IL-6,p-NF-κB p65 protein expression in wound tissue were increased(P<0.05).Compared with the model group,the state of rats was gradually improved in the Huangqi Yanghe Decoction low and high dose groups,and the lesion degree of wound tissue was reduced successively,wound healing rate,TcpO2 in wound surrounding tissue,serum VEGF,HIF-1α,microvascular density,p-PI3K,p-AKT and IκB-α protein expression levels in wound tissue were increased in turn(P<0.05).The FBG,serum CRP,IL-6 and p-NF-κB p65 protein expression in wound tissue were decreased in turn(P<0.05).LY294002 could partially reverse the therapeutic effect of high-dose Huangqi Yanghe Decoction on DFU rats(P<0.05).Conclusion Huangqi Yanghe Decoction can regulate PI3K/AKT/NF-κB pathway,inhibit inflammatory response in DFU rats,promote angiogenesis and thus promote wound healing.
5.Changes and biological significance of ferroptosis in a mouse model of bloodstream infection induced by different bacteria
Zhibin ZHANG ; Chu WANG ; Ying HAN ; Jia WANG ; Junqing LYU ; Xuerong LIN ; Meng YUAN ; Shuchi HAN
Chinese Journal of Tissue Engineering Research 2024;28(28):4553-4558
BACKGROUND:It is of great significance to find new diagnostic markers of the disease and molecular targets for the treatment of the disease and the alleviation of organ injury.Ferroptosis is a newly discovered form of cell death.Overactivation of ferroptosis in animal models of sepsis is associated with the activation of inflammatory response and the injury of the liver,heart,kidney and other important organs,but the relationship between ferroptosis and bloodstream infection is not very clear. OBJECTIVE:To study the changes and biological significance of ferroptosis in a mouse model of blood stream infection induced by different bacteria. METHODS:Blood stream infection models induced by gram negative bacteria Escherichia coli,Klebsiella pneumoniae and gram positive bacteria Staphylococcus aureus and Enterococcus faecalis were established in SPF-grade ICR male mice,with 42 mice in each group.The mRNA expression levels of ferroptosis marker genes transferrin receptor 1 and glutathione peroxidase 4 in the liver,myocardium and kidney were detected at 0.5,1,3,6,12,24 and 48 hours after modeling.Another 18 SPF-grade ICR male mice were selected and randomly divided into dimethyl sulfoxide(DMSO)control group,DMSO+Klebsiella pneumoniae group,and Ferrostatin-1+Klebsiella pneumoniae group,with 6 mice in each group.In the latter two groups,animal models of Klebsiella pneumoniae bloodstream infection were established by tail vein injection of Klebsiella pneumoniae suspension,and 5 mg/kg Ferrostatin-1 and an equal dose of DMSO were given intraperitoneally 1 hour prior to the modeling of bloodstream infection,respectively.Serum levels of alanine aminotransferase,aspartate aminotransferase,blood creatinine,blood urea nitrogen,phosphocreatine kinase isoenzyme,lactate dehydrogenase,and mRNA expression levels of ferroptosis marker genes in various tissues were assayed at 6 hours after modeling. RESULTS AND CONCLUSION:After bloodstream infection modeling,the mRNA expression levels of transferrin receptor 1 in the liver,myocardium and kidney of bloodstream infection mice with different bacteria increased first and then decreased;and the mRNA expression level of glutathione peroxidase 4 decreased first,then increased,and reached the peak at 6 hours after modeling.The changes in transferrin receptor 1 and glutathione peroxidase 4 mRNA levels in bloodstream infection mice induced by gram-negative bacteria were more significant than those in blood stream infection mice induced by gram-positive bacteria,especially in bloodstream infection mice induced by Klebsiella pneumoniae.At 6 hours after bloodstream infection induced by Klebsiella pneumoniae,the levels of alanine aminotransferase,aspartate aminotransferase,serum creatinine,blood urea nitrogen,creatine phosphate kinase isoenzyme,lactate dehydrogenase in mice were significantly increased.Before modeling,Ferrostatin-1 intervention significantly reduced the levels of alanine aminotransferase,aspartate aminotransferase,serum creatinine,blood urea nitrogen,creatine phosphate kinase isoenzyme,and lactate dehydrogenase.All these findings indicate that the activation of ferroptosis in bloodstream infection mice induced by different bacteria is obvious,and the activation of ferroptosis in bloodstream infection mice induced by gram-negative bacteria is more obvious.Inhibition of iron death significantly attenuates liver,myocardial,and kidney injury in the mouse model of bloodstream infection induced by Klebsiella pneumoniae.
6.Three internal fixation devices used for finite element analysis of Pauwels type Ⅲ femoral neck fractures
Yuanbo QI ; Jiantao LI ; Daohong LIU ; Sheng TAO ; Daofeng WANG ; Jie WU
Chinese Journal of Tissue Engineering Research 2024;28(30):4763-4769
BACKGROUND:At present,there is still controversy in clinical practice about the choice of internal fixation of Pauwels type Ⅲ femoral neck fracture,and the selection of internal fixation that provides stable fixation strength is the key basis for achieving Pauwels type Ⅲ fracture fixation. OBJECTIVE:The three-dimensional finite element analysis method was used to test the difference in biomechanical strength of three types of internal fixation in Pauwels type Ⅲ femoral neck fracture,which provided a reference for its clinical treatment. METHODS:Using the CT data of the left femur of a healthy male volunteer,a complete femur and its cancellous bone were reconstructed in Mimics software,and Geomagic studio software was used for reverse modeling.Cannulated compression screw,dynamic hip screw,and femoral neck system were created in UG-NX software.Three kinds of internal fixation models were assembled on the femur model,and Pauwels type Ⅲ femoral neck fracture was simulated by Hypermesh software.Finally,Abaqus software was used to carry out finite element experimental analysis to analyze and compare the stress distribution,stress peak,strain,and displacement distribution caused by fixed femoral neck fracture of different internal fixation systems. RESULTS AND CONCLUSION:(1)The stress of the proximal femur bone mass was mainly distributed in the area below the femoral neck near the fracture end,with the highest stress peak in the dynamic hip screw group and the smallest in the femoral neck system group.(2)The stress distribution of the internal fixation device was mainly concentrated on the screw surface near the fracture line,with the highest stress peak in the femoral neck system group and the smallest in the dynamic hip screw group.(3)The main strain field of the proximal femur bone mass was distributed in the upper surface area where the bone and screw contacted,and the yield strain was the smallest in the femoral neck system group and the largest in the cannulated compression screw group.(4)The main strain field of the internal fixation device model was distributed on the upper surface of the femoral neck screw,with the yield strain being the smallest in the femoral neck system group and the largest in the cannulated compression screw group.(5)The displacement distribution values of femur,proximal bone mass,distal bone block,internal fixation device and internal fixation with the femur as a whole in the three femoral neck fracture internal fixation models decreased gradually from proximal to distal,and the peak displacement of the femoral neck system group was the largest and the lowest in the dynamic hip screw group.(6)The results showed that when the Pauwels type Ⅲ femoral neck fracture was fixed,the stress distribution of femoral neck system was more uniform,the mechanical conduction characteristics were better,and it was subjected to lower yield strain,higher stress and higher displacement.It has relatively better biomechanical stability and can provide a superior mechanical environment for fracture healing.
7.The Relationship between the Duration of Folic Acid Supplementation,Gesta-tional Diabetes Mellitus and Adverse Perinatal Outcomes
Jinyi WANG ; Chunxing MA ; Yueyue GAO ; Yaming ZHANG ; Fengying WANG ; Xuntao LIU ; Yunchun LIU
Journal of Practical Obstetrics and Gynecology 2024;40(8):664-669
Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55%)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89%)receiving folic acid supplementation during pregnancy and 496 patients(65.35%)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14%.Compared with those who received folic acid supplementation before pregnancy for<3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95%CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95%CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95%CI 1.06-1.75))and macrosomia(aRR2.11,95%CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95%CI 1.01-2.34)and 2.43(95%CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P<0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.
8.The Relationship between the Duration of Folic Acid Supplementation,Gesta-tional Diabetes Mellitus and Adverse Perinatal Outcomes
Jinyi WANG ; Chunxing MA ; Yueyue GAO ; Yaming ZHANG ; Fengying WANG ; Xuntao LIU ; Yunchun LIU
Journal of Practical Obstetrics and Gynecology 2024;40(8):664-669
Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55%)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89%)receiving folic acid supplementation during pregnancy and 496 patients(65.35%)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14%.Compared with those who received folic acid supplementation before pregnancy for<3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95%CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95%CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95%CI 1.06-1.75))and macrosomia(aRR2.11,95%CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95%CI 1.01-2.34)and 2.43(95%CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P<0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.
9.The Relationship between the Duration of Folic Acid Supplementation,Gesta-tional Diabetes Mellitus and Adverse Perinatal Outcomes
Jinyi WANG ; Chunxing MA ; Yueyue GAO ; Yaming ZHANG ; Fengying WANG ; Xuntao LIU ; Yunchun LIU
Journal of Practical Obstetrics and Gynecology 2024;40(8):664-669
Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55%)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89%)receiving folic acid supplementation during pregnancy and 496 patients(65.35%)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14%.Compared with those who received folic acid supplementation before pregnancy for<3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95%CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95%CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95%CI 1.06-1.75))and macrosomia(aRR2.11,95%CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95%CI 1.01-2.34)and 2.43(95%CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P<0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.
10.The Relationship between the Duration of Folic Acid Supplementation,Gesta-tional Diabetes Mellitus and Adverse Perinatal Outcomes
Jinyi WANG ; Chunxing MA ; Yueyue GAO ; Yaming ZHANG ; Fengying WANG ; Xuntao LIU ; Yunchun LIU
Journal of Practical Obstetrics and Gynecology 2024;40(8):664-669
Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55%)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89%)receiving folic acid supplementation during pregnancy and 496 patients(65.35%)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14%.Compared with those who received folic acid supplementation before pregnancy for<3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95%CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95%CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95%CI 1.06-1.75))and macrosomia(aRR2.11,95%CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95%CI 1.01-2.34)and 2.43(95%CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P<0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.

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